Gabapentin

Description

Pregabalin is a gabapentinoid drug used for the treatment of focal seizures and peripheral neuropathic pain. Sometimes, pregabalin is prescribed for the treatment of symptoms of multiple sclerosis, motor neurone disease, and menopause for people with breast cancer. Its main clinical effects are anticonvulsant (mostly used in focal onset seizures) and antihyperalgesic (reversing an increased pain sensitivity).

Pharmacology

Similar to pregabalin, gabapentin produces anticonvulsant (mostly used in focal onset seizures) and antihyperalgesic (reversing an increased pain sensitivity) effects. These effects are a result of gabapentin’s action on calcium signals in the nervous system which are important in linking together the electrical and chemical messages in the brain, heart, and muscles.

Gabapentin is a longer onset, shorter acting gabapentinoid compared to pregabalin. The drug was originally designed to mimic the inhibitory neurotransmitter GABA. However, later research found that, unlike benzodiazepines and alcohol, gabapentin does not directly affect GABA receptors. Instead, gabapentin is thought to reduce the amount of calcium that enters neurons (nerve cells) through blocking α2δ-1/2 calcium channel subunits, leading to less neurotransmitter release, resulting in a reduction in seizures and pain signals in the brain.

Gabapentin’s antihyperalgesic effects are thought to be caused by a reduction in levels of calcium channel proteins in nerve cells, which increase after nerve damage leading to mild sensations feeling painful.

Gabapentin’s significant anticonvulsant properties are thought to involve regulation of calcium levels within nerve cells (neurons) and in the tiny gaps existing between neurons in the central nervous system (CNS) called ‘synapses’.

Its muscle-relaxant properties are thought to be caused by its inhibition of chemical pathways that ordinarily occur within the spinal cord.

Interactions

The combination of gabapentin with other depressants, such as opioids and benzodiazepines, is associated with an increase in respiratory depression and overdose. As opioid tolerance leads to more calcium channels in nerve cells, pregabalin has been shown to reverse opioid tolerance which can lead to accidental overdose. Drinking alcohol alongside taking gabapentin can lead to increased sedative effects on the brain and body.

Harm Reduction

• Start low, go slow: Take a small amount and wait until you can feel the effects before taking more/anything else
• Try not to use alone: If something goes wrong, someone is there to get help
• Be careful mixing: Mixing gabapentin with other depressants increases overdose risk – avoid if you can, otherwise take less of each, as they can increase the effects and risks
• Carry naloxone: In case opioids are in the mix
• Test your stuff: Find out how to send a sample to WEDINOS for testing here: https://www.wedinos.wales or pick up some test strips at our Harm Reduction Hub
• If you’ve been prescribed gabapentin and you notice a tolerance starting to develop (you need to keep taking more to get the same effect) speak to your doctor – don’t just start increasing your dose yourself.
• Don’t suddenly stop taking them, or you may start to experience symptoms of withdrawal: these can range from a return of your original symptoms (possibly even worse than before) to totally new symptoms.
• If you have become physically dependent on gabapentin, the symptoms of abruptly stopping are likely to be even worse. It’s important to get proper medical advice on how to reduce your intake slowly.
• It’s also possible to become psychologically dependent on the drug (feeling like you need it all the time). If you think this is happening, see your doctor as soon as possible, but don’t suddenly stop taking it.

History

Gabapentin was developed in 1976 by Gerhard Satzinger and colleagues at German pharmaceutical company Goedecke AG, where they were attempting to develop anti-epileptic drugs that mimicked the effects of the inhibitory neurotransmitter GABA. Gabapentin easily enters the brain and passes through the body unmetabolised, which was thought to make it an ideal drug with minimal side effects or drug interactions.

In 1993, gabapentin (Neurontin) was marketed for add-on treatment of epilepsy. By the mid-90s it was well known that anti-epileptics also improved treatment-resistant neuropathic pain. By 2001, 83% of Neurontin prescriptions were for non-epilepsy conditions that it was not approved to treat. As confidence in prescribing benzodiazepines for conditions such as epilepsy and anxiety decreased, gabapentinoid prescriptions rose to meet patients’ needs.

In the 2000–2010s, its inducement of physical dependence and respiratory depressant effects garnered increased attention. Growing concern around the non-prescribed use of pregabalin and gabapentin, particularly in Northern Ireland and prison populations, came as gabapentinoid-related deaths rose across the UK and Europe. This led to the NHS and Public Health England warning prescribers about these issues, although British doctors still issue over 7 million prescriptions for it per year.

Non-prescribed sales of gabapentin have increased to meet demands from people using the drug for a variety of reasons. These include use to induce the expected clinical effects, taking higher doses to achieve a ‘high’ or by those already with a dependency, combined use with other depressant drugs.

Law

• Class C
  • Schedule 3

Possible offences

• Possession
  • Maximum sentence – 2 years/fine/both
• Possession With Intent To Supply
  • Maximum sentence – 14 years/fine/both
• Supply (including being concerned in supply, conspiracy to supply, aggravated supply and offer to supply)
  • Maximum sentence – 14 years/fine/both
• Production
  • Maximum sentence – 14 years/fine/both

In practice maximum sentences are rarely used, for more detailed and accurate information go to our sentencing page.